379MO - Homologous recombination deficiency testing in Vietnamese patients with ovarian cancer

Background

Assessing homologous recombination deficiency (HRD) status has been recommended by clinical guidelines for patients with ovarian cancer (OC) as it predicts sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). However, HRD testing is complex and either inaccessible or unaffordable for majority of OC patients in developing countries. Consequently, the prevalence of HRD in OC remains unknown.

Methods

We examined HRD status of 77 Vietnamese patients with advanced OC using a laboratory-developed test (HRD Insight, Gene Solutions, Vietnam). Tumor DNA was extracted from FFPE samples, followed by next-generation sequencing to detect deleterious or suspected deleterious variants in BRCA1 and BRCA2 genes. Shallow whole genome sequencing was performed to determine the whole Genomic Instability (wGI) score by assessing the presence of large-scale intra-chromosomal copy number alterations.

Results

The successful rate of HRD testing was 94.8% (73/77) and minimal input was 8 ng DNA. HRD-positive status was found in 54.8% (40/73) of OC patients. The BRCA1/2 mutational rate was 19.2% (14/73) while the rate of genomic instability established by high wGI scores was 47.9% (35/73). For analytical validation, the HRD Insight assay was benchmarked with commercial kits including TruSight Oncology 500 HRD (Illumina), SOPHiA DDM HRD Solutions (Sophia Genetics) and HRD Focus Panel (AmoyDx) to determine HRD status of the 44 samples. Compared with the 3 kits, our assay showed a concordance rate of 94.6%, positive percent agreement and negative percent agreement of 96.4% and 92.9% respectively.

Conclusions

HRD status could be accurately and reliably determined by our HRD Insight assay to help physicians select approved PARPi for OC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Gene Solutions JSC, Ho Chi Minh, Viet Nam.

Disclosure

All authors have declared no conflicts of interest.